Cognitive function is related to fronto-striatal serotonin transporter levels – a brain PET study in young healthy subjects

Madsen, Karine; Erritzoe, D.; Mortensen, Erik Lykke; Gade, Anders; Madsen, Jacob; Baaré, William F.C.; Knudsen, Gitte M.; Hasselbalch, Steen G.

doi:10.1007/s00213-010-1926-4

Cited by 41 publications

(33 citation statements)

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“…However, LSD also affected the performance in the congruent conditions (cards A and B), even though the effect was most pronounced in the conflict condition (card C; Krus et al, 1963;Wapner and Krus, 1960). That the 5-HT system is crucially involved in processes involved in the performance of the Stroop Test has been shown by several studies: (1) acute tryptophan depletion reduces RT interference in the Stroop Test (Evers et al, 2006;Schmitt et al, 2000;Scholes et al, 2007); (2) performance in the conflict condition of the Eriksen Flanker Task (Reuter et al, 2007) as well as in congruent conditions of the Stroop Test (Osinsky et al, 2009) depends on a promoter polymorphism of the tryptophan-hydroxylase 2 gene (TPH2 -703 G/T), which has an impact on 5-HT synthesis (Invernizzi, 2007); and (3) Stroop interference was correlated with the 5-HT transporter density within the DLPFC measured with [ 11 C]DASB positron emission tomography (PET; Madsen et al, 2011). Based on the present findings, we speculate that deficits in conflict monitoring and response inhibition in schizophrenia might be caused by changes in 5-HT 2A RFan assumption that might be supported by the finding that the 5-HT 2A/2B/2C , 5-HT 1A , and 5-HT 7 R antagonist cyproheptadine improved RT in the conflict condition of the Stroop Test in chronic schizophrenia patients (Chaudhry et al, 2002), whereas the partial 5-HT 1A R agonist buspirone had no effect on Stroop performance in a comparable patient population (Piskulic et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Quednow¹,

Kometer²,

Geyer

et al. 2011

Neuropsychopharmacol

187

120

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The serotonin-2A receptor (5-HT(2A)R) has been implicated in the pathogenesis of schizophrenia and related inhibitory gating and behavioral inhibition deficits of schizophrenia patients. The hallucinogen psilocybin disrupts automatic forms of sensorimotor gating and response inhibition in humans, but it is unclear so far whether the 5-HT(2A)R or 5-HT(1A)R agonist properties of its bioactive metabolite psilocin account for these effects. Thus, we investigated whether psilocybin-induced deficits in automatic and controlled inhibition in healthy humans could be attenuated by the 5-HT(2A/2C)R antagonist ketanserin. A total of 16 healthy participants received placebo, ketanserin (40 mg p.o.), psilocybin (260 μg/kg p.o.), or psilocybin plus ketanserin in a double-blind, randomized, and counterbalanced order. Sensorimotor gating was measured by prepulse inhibition (PPI) of the acoustic startle response. The effects on psychopathological core dimensions and behavioral inhibition were assessed by the altered states of consciousness questionnaire (5D-ASC), and the Color-Word Stroop Test. Psilocybin decreased PPI at short lead intervals (30 ms), increased all 5D-ASC scores, and selectively increased errors in the interference condition of the Stroop Test. Stroop interference and Stroop effect of the response latencies were increased under psilocybin as well. Psilocybin-induced alterations were attenuated by ketanserin pretreatment, whereas ketanserin alone had no significant effects. These findings suggest that the disrupting effects of psilocybin on automatic and controlled inhibition processes are attributable to 5-HT(2A)R stimulation. Sensorimotor gating and attentional control deficits of schizophrenia patients might be due to changes within the 5-HT(2A)R system.

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Section: Discussionmentioning

confidence: 99%

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Quednow¹,

Kometer²,

Geyer

et al. 2011

Neuropsychopharmacol

187

120

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“…SERT binding in the hypothalamus was observed to be negatively associated with pain (Kupers et al 2011), while cognitive functioning was found to be positively correlated to SERT levels in right dorsolateral PFC, caudate and left ventrolateral PFC (Madsen et al 2011a). Another negative association was found between SERT binding in the thalamus and stress and anxiety (Ichise et al 2006;Reimold et al 2011).…”

Section: Transportersmentioning

confidence: 95%

Serotonin and molecular neuroimaging in humans using PET

2011

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The serotonergic system is one of the most important modulatory neurotransmitter systems in the human brain. It plays a central role in major physiological processes and is implicated in a number of psychiatric disorders. Along with the dopaminergic system, it is also one of the phylogenetically oldest human neurotransmitter systems and one of the most diverse, with 14 different receptors identified up to this day, many of whose function remains to be understood. The system's functioning is even more diverse than the number of its receptors, since each is implicated in a number of different processes. This review aims at illustrating the distribution and summarizing the main functions of the serotonin (5-hydroxytryptamin, 5-HT) receptors as well as the serotonin transporter (SERT, 5-HTT), the vesicular monoamine transporter 2, monoamine oxidase type A and 5-HT synthesis in the human brain. Recent advances in in vivo quantification of these different receptors and enzymes that are part of the serotonergic system using positron emission tomography are described.

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“…We have been particularly interested in how individual differences in healthy volunteers may serve as important predictors of vulnerability to neuropsychiatric disorders, including personality traits (da Cunha-Bang et al, 2013;Frokjaer et al, 2008;Kalbitzer et al, 2009), affective disorders Frokjaer et al, 2009Macoveanu et al, 2014;Madsen et al, 2014) and memory disorders (Haahr et al, 2013;Madsen et al, 2011c;Madsen et al, 2011a). We have primarily chosen to investigate healthy volunteers in order to exclude confounds such as medication bias and scar effects from prior disease processes and to separate trait and state factors.…”

Section: Introductionmentioning

confidence: 99%

The Center for Integrated Molecular Brain Imaging (Cimbi) database

et al. 2016

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We here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes. The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies. The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank.

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Cognitive function is related to fronto-striatal serotonin transporter levels – a brain PET study in young healthy subjects

Abstract: The results imply that in healthy subjects, high SERT binding in fronto-striatal regions is associated with better performance on tasks involving executive function and logical reasoning.

Cited by 41 publications

References 50 publications

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Psilocybin-Induced Deficits in Automatic and Controlled Inhibition are Attenuated by Ketanserin in Healthy Human Volunteers

Serotonin and molecular neuroimaging in humans using PET

The Center for Integrated Molecular Brain Imaging (Cimbi) database

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